摘要
目的 检测空泡蛋白分类相关蛋白33A(vacuolar protein sorting-associated protein 33A,VPS33A)在老年肺结核患者外周血中的表达情况,并探讨其与临床预后的相关性.方法 收集麻城市人民医院2019年2月～2021年2月收治的95例老年肺结核患者为研究组,另外选取同期健康体检者90例为对照组.采用实时荧光定量PCR(qRT-PCR)检测外周血中VPS33A,Toll样受体2(TLR2)表达情况,酶联免疫吸附法(ELISA)检测外周血中白细胞介素-6(IL-6)水平.肺结核患者给予标准化抗结核方案治疗(2HRZE/4HR),治疗后随访12个月,根据患者预后将其分为预后良好组(n=58)和预后不良组(n=37),采用受试者工作特征(ROC)曲线分析VPS33A对患者预后不良的预测价值;Pearson法分析预后不良组血清VPS33A与IL-6,TLR2的相关性;Logistic回归分析老年肺结核患者预后不良的影响因素.结果 与对照组比较,治疗前研究组外周血VPS33A(0.87±0.22 vs 1.02±0.23)水平明显降低,IL-6(22.13±5.36 pg/mlvs 18.53±4.68pg/ml),TLR2(1.26±0.25 vs 0.99±0.21)水平明显升高,差异具有统计学意义(t=6.170,6.682,11.241,均P＜0.05);与治疗前研究组比较,治疗后研究组外周血VPS33A(0.95±0.25)水平明显升高,IL-6(19.66±5.44 pg/ml),TLR2(1.11±0.2)水平明显降低,差异具有统计学意义(t=3.336,4.648,6.331,均P＜0.05).预后不良组外周血 VPS33A 水平(0.71±0.16)显著低于预后良好组(0.97±0.22);IL-6(26.41±7.16 pg/ml),TLR2(1.35±0.26)水平显著高于预后良好组(19.40±4.21 pg/ml,1.20±0.24),差异具有统计学意义(t=5.555,6.012,2.875,均P＜0.05).经Pearson法分析发现,治疗前外周血VPS33A分别与IL-6,TLR2水平呈负相关(r=-0.649,-0.634,均P＜0.05).ROC曲线分析结果显示VPS33A,IL-6和TLR2预测老年肺结核预后的AUC分别为0.805,0.842和0.882,三者联合 AUC 为 0.971,明显高于三者单独预测(Z=4.010,3.136,2.285,P=0.001,0.002,0.022);Logistic 回归分析显示外周血VPS33A,IL-6和TLR2是老年肺结核患者预后不良的影响因素(均P＜0.05).结论 VPS33A在老年肺结核患者外周血中的表达下调,对老年肺结核患者预后有较好的预测价值,且是预后不良的影响因素.
Abstract
Objective To detect the expression of vacuolar protein sorting-associated protein 33A(VPS33A)in the peripheral blood of elderly patients with pulmonary tuberculosis,and explore its correlation with clinical prognosis.Methods A total of 95 elderly pulmonary tuberculosis patients admitted to Macheng City People's Hospital from February 2019 to February 2021 were collected as the research group,and 90 healthy subjects in the same period were selected as control group.The expression of VPS33A and Toll like receptor 2(TLR2)in peripheral blood was detected by real-time fluorescent quantitative PCR(qRT-PCR),and the level of interleukin-6(IL-6)in peripheral blood was detected by enzyme-linked immunosorbent assay.Patients with pulmonary tuberculosis were given standardized anti-tuberculosis regimen therapy(2HRZE/4HR)treatment,and they were followed up for 12 months.According to their prognosis,they were divided into good prognosis group(n=58)and bad prognosis group(n=37).The predictive value of VPS33A for poor prognosis was analyzed by ROC curve.The correlation between serum VPS33A,IL-6 and TLR2 in poor prognosis group was analyzed by Pearson method.Logistic regression analysis was used to explore the factors influencing poor prognosis in elderly patients with pulmonary tuberculosis.Results Compared with the control group,VPS33A level(0.87±0.22 vs 1.02±0.23)in peripheral blood was lower,but IL-6(22.13±5.36 pg/ml vs 18.53±4.68 pg/ml)and TLR2 levels(1.26±0.25 vs 0.99±0.21)were higher in the pre-treatment study group,with significant differences(t=6.170,6.682,11.241,all P＜0.05).Compared with the pre-treatment study group,VPS33A level(0.95±0.25)in peripheral blood was higher,but IL-6(19.66±5.44 pg/ml)and TLR2 levels(1.11±0.2)were lower in the post-treatment study group,with significant differences(t=3.336,4.648,6.331,all P＜0.05).The level of VPS33A(0.71±0.16)in peripheral blood of poor prognosis group was lower than that of good prognosis group(0.97±0.22),while the levels of IL-6(26.41±7.16 pg/ml)and TLR2(1.35±0.26)were higher than those of good prognosis group(19.40±4.21pg/ml,1.20±0.24),with significant differences(t=5.555,6.012,2.875,all P＜0.05).Pearson correlation analysis showed that VPS33A in the pre-treatment study group was negatively correlated with IL-6 and TLR2 levels(r=-0.649,-0.634,all P＜0.05).ROC curve analysis results showed that the AUCs of VPS33A,IL-6 and TLR2 for predicting the prognosis of tuberculosis in the elderly were 0.805,0.842 and 0.882,respectively.The combined AUC of the three was 0.971,which was higher than that predicted by the three alone(Z=4.010,3.136,2.285,P=0.001,0.002,0.022).Logistic regression analysis showed that VPS33A,IL-6 and TLR2 were the influencing factors for poor prognosis of elderly pulmonary tuberculosis patients(all P＜0.05).Conclusion The expression of VPS33A is down-regulated in the peripheral blood of elderly patients with pulmonary tuberculosis,which may be a good predictive value for the prognosis of elderly patients with pulmonary tuberculosis,and be a factor affecting bad prognosis.
维普
万方数据